Our work is aimed at elucidating the neurochemical mechanisms responsible for the development of ethanol tolerance. The development of tolerance has been postulated to substantially influence the quantity of alcohol consumed by an individual and an individual's drinking patterns. We will first establish a conceptual framework within which phenomena such as acute tolerance, chronic tolerance and ethanol sensitivity can be investigated. Studies will then be performed to establish pharmacologic means of modulating tolerance development and such studies will extend our prior work which showed that normal function of noradrenergic neurons of brain is necessary for tolerance development. Our earlier work also indicated that certain forms of tolerance may be encoded in dopaminergic neurons of brain, and we propose to perform an in-depth analysis of the function of dopamine systems of the ethanol-tolerant animal. Finally, we will address the issue of whether a single adaptive process such as a change in neuronal membrane structure is responsible for all forms of functional tolerance or whether system-specific adaptive responses determine the phenomenon of ethanol tolerance.